Artemisinin is an antimalarial substance very sparingly soluble in water. In the attempt to identify
environmental-friendly and non-toxic aqueous-based solvents to extract it from Artemisia annua L., the solubility
of artemisinin in aqueous solutions of different hydrotropes was measured at 303.2 K, for hydrotrope concentrations
up to 5 M. The ability of the studied hydrotropes for enhancing the artemisinin solubility increases in the
following order: Na[N(CN)2] < Na[SCN] < [Chol][Van] < [Chol][Gal] < [N4,4,4,4]Cl < [Chol][Sal] < [P4,4,4,4]Cl
< Na[Sal], with Na[Sal] allowing an increase in the solubility of 750 fold compared to pure water.
The COSMO-RS model and experimental Kamlet-Taft solvatochromic parameters were applied to connect the
solubility enhancement with solvent properties. At low hydrotrope concentration, the solubility increases with
the decreasing of the difference between the Apolar Factors of the hydrotrope and artemisinin, while for higher
hydrotrope concentration, the hydrogen-bond acceptor character of the hydrotrope seems to have an impact on
the solubility enhancement. Even if some mechanistic understanding is still to unfold, quantitatively the
empirical correlations of solubility enhancement with the hydrotrope concentration and the solvatochromic
parameters show very high accuracy. In particular, 93% of the change on the artemisinin solubility enhancement
could be explained using the hydrotrope concentration and two combined solvatochromic parameters (αβ and
π∗2) as explaining variables.This work was developed within the scope of the projects CICECOAveiro
Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020,
CIMO-Mountain Research Center, UIDB/00690/2020, and Green Health
(Norte-01-0145-FEDER-000042) all financed by national funds through
the FCT/MEC and when appropriate co-financed by FEDER under the
PT2020 and NORTE 2020 Partnership Agreement. Isabela Sales and
Silvana Mattedi thanks the finantial support from CAPES and CNPq/
Brazil (CAPES: Proc. 88881.189075/2018-01 and 88887.494428/2020-
00. CNPq: Grant 303089/2019-9 and Proc.438036/2018-2).info:eu-repo/semantics/publishedVersio